Electromagnetic modulation of the ALS transcriptome: towards a non-drug molecular cure

Using compartmentalized neuron cultures, we also tested different magnetic field orientations relative to axons. Following ACMS, we assessed axonal organelle trafficking and the nuclear DNA damage response (DDR) by live-cell imaging. Untreated ALS neurons showed clear defects in both assays.

Exposure to magnetic AC sine waves above a threshold of 7 mT, applied perpendicular to the axonal plane with an optimal low frequency of 25 Hz, led to a sustained boost of mitochondrial and lysosomal motility for over one week and rehabilitaiton of DDR. These phenotypic improvements correlated with global transcriptomic changes revealed by RNA-sequencing. While untreated mutant and wild-type neurons displayed distinct gene expression profiles, ACMS induced a novel, harmonized profile across all lines.

Differential gene expression analysis suggests that ACMS activates extracellular matrix (ECM)-mediated cell adhesion and triggers neurotransmitter receptors, ion channels and kinase signaling pathways, ultimately altering gene transcription and, thereby, motor and microtubule-associated proteins. Our results highlight ACMS as a promising non-invasive, non-pharmacological treatment for neurodegenerative diseases.